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N A Saunders

Publications and source records attributed to N A Saunders.

At least 73 records · Page 4Linked to original sources
PubMed1993

Regulation of proliferation-specific and differentiation-specific genes during senescence of human epidermal keratinocyte and mammary epithelial cells.

The expression of proliferation-associated genes, cdc2 and E2F-1 and squamous-specific genes transglutaminase type I and cornifin were examined in senescing human epidermal keratinocytes. Cultured keratinocytes underwent 34 population doublings before senescing. Senescence in keratinocytes was characterised by reduced thymidine incorporation, a change in morphology and the inability of cells to undergo mitosis. This was accompanied by downregulation of cdc2 and E2F-1 mRNA's. In addition, senescing keratinocytes started to express genes such as cornifin, that are specific for squamous differentiation. These changes were similar to those observed in keratinocytes induced to differentiate with phorbol ester or by confluence. E2F-1, cdc2 and cornifin were similarly altered in senescing human mammary epithelial cells. Our data suggest that events regulating senescence may also be linked to squamous differentiation.

Base Sequence↗
PubMed1993

Phylogenic homogeneity of Coxiella burnetii strains as determinated by 16S ribosomal RNA sequencing.

DNA coding for the 16S rRNA of six strains of the obligate intracellular bacterium Coxiella burnetii was directly amplified from lysed host cells using the polymerase chain reaction. The amplification product was sequenced using a linear-PCR procedure and compared with other published 16S rRNA sequences. The results of this analysis confirm the position of C. burnetii in the gamma subgroup of the proteobacteria. The data show that all of the C. burnetii strains are highly related (> 99%) on the basis of 16S rRNA sequences although they had different geographic origins and phenotypic characteristics. The data support a phylogenetic homogeneity of the genus Coxiella with only one species which is C. burnetii.

Base Sequence↗
PubMed1993

A comparison of clinical assessment and home oximetry in the diagnosis of obstructive sleep apnea.

In order to determine whether measurement of arterial oxygen saturation (SaO2) could identify patients with obstructive sleep apnea (OSA), 98 consecutive patients referred for assessment of snoring and/or daytime somnolence were assessed clinically and then underwent both unsupervised oximetry in their homes and formal polysomnography. Clinical assessment identified patients with an apnea+hypopnea index (AHI) > or = 15 events per hour with a sensitivity of 79% and a specificity of 50%. Home oximetry analyzed by counting the number of arterial oxygen desaturations recorded was inferior to clinical assessment. For desaturations of 2% or more from baseline, desaturation index (DI) > or = 15 per hour identified patients with AHI > or = 15 with sensitivity 65% and specificity 74%; for 3% desaturations, sensitivity was 51% and specificity 90%; and for 4% desaturations, sensitivity was 40% and specificity 98%. From the oximetry data, the percentage of time spent at SaO2 below 90% (CT90) was also calculated. CT90 > or = 1% identified patients with AHI > or = 15 with sensitivity 93% and specificity 51%; for patients with AHI > or = 15 ultimately given nasal continuous positive airway pressure (CPAP), the sensitivity of a CT90 > or = 1% was 100%. We concluded that home oximetry with CT90 < 1% practically excludes clinically significant OSA. Conversely, home oximetry with DI > or = 15 for 4% desaturations makes OSA likely: the positive predictive value for OSA is 83% if the pretest probability of OSA is 30% and over 90% if the pretest probability is at least 50%.

Adult↗
PubMed1993

Regulation of transglutaminase type I expression in squamous differentiating rabbit tracheal epithelial cells and human epidermal keratinocytes: effects of retinoic acid and phorbol esters.

In the present study we describe the full length cDNA sequence for rabbit transglutaminase type I as well as the sequence for a 2.9-kilobase (kb) promoter fragment of the gene. Transglutaminase type I mRNA expression was inhibited in squamous differentiating epithelia by retinoic acid (RA) in a dose-dependent (EC50 = 1-2 nM) and transcriptional manner. In human epidermal keratinocytes transglutaminase type I mRNA was induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment, and this induction could be inhibited by bryostatin 1. In contrast, TPA treatment inhibited the expression of c-myc mRNA. Bryostatin 1 but not RA could prevent this decrease in c-myc mRNA expression, indicating that transglutaminase type I mRNA expression was associated with differentiation and not growth arrest. An SP1 element was found within 50 base pairs 5' of the transcription initiation site. A TATA-like element (CATAAAC) was found but was not capable of activating transcription. In addition, putative response elements for C-MYC, Ker1/AP2, 2 AP1 sites, a CK-8-mer, and an AP2 site were present in the 2.9-kb fragment. Transfection of RbTE cells with the 2.9-kb fragment ligated to a promoterless luciferase vector resulted in 2.2-fold more luciferase expression in differentiated vs. undifferentiated cells. Furthermore, luciferase activity was induced 7.4-fold in human epidermal keratinocytes induced to differentiate with TPA. TPA-induced luciferase activity was inhibited by both bryostatin 1 and RA. No known RA response elements were identified in the promoter.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

Cornifin, a cross-linked envelope precursor in keratinocytes that is down-regulated by retinoids.

In this study, we have characterized the cDNA clone SQ37 that was isolated previously from a rabbit squamous cell library. The gene encodes a 14-kDa protein that appears to function as a component of the cross-linked envelope in squamous differentiating cells. The protein, which has been named cornifin, has a high content of proline (31%), glutamine (20%), and cysteine (11%) and contains 13 repeats of an octapeptide (consensus sequence, EPCQPKVP) at its C terminus. SQ37 mRNA and protein are induced during squamous differentiation of rabbit tracheal (RbTE) cells and human epidermal keratinocytes. This induction is repressed by retinoids. Immunohistochemical studies reveal SQ37 immunoreactivity in fragmented cross-linked envelopes from squamous-differentiated RbTE cells and in the suprabasal layers of the epidermis. In situ hybridization analysis showed that the presence of SQ37 mRNA is restricted to the suprabasal layers. Treatment of RbTE cells with a Ca2+ ionophore induces cross-linking of the SQ37 protein into higher molecular weight complexes. This cross-linking reaction appears to be mediated by transglutaminase type I. Our observations suggest that the protein encoded by SQ37 participates in the assembly of the cross-linked envelope.

Amino Acid Sequence↗
PubMed1992

Neuropsychological functioning and sleep patterns in the elderly.

OBJECTIVE: To discover whether reported sleep-wake disturbances in the elderly (more frequent nocturnal awakenings, earlier waking and more day time naps) are associated with neuropsychological dysfunction. DESIGN AND SETTING: A sample of 124 residents of a retirement village complex were interviewed about their sleep patterns and given neuropsychological assessments. Reported sleep-wake difficulties were combined to form two variables, "night sleep" and "day sleep". Additional sleep variables analysed were reported sleep duration and time of wakening. Principal components analysis of the neuropsychological test scores yielded four factors: "general ability", "memory", "motor", and "cerebral efficiency". MAIN OUTCOME MEASURES: A correlation analysis was performed for sleep variables, neuropsychological factors and age, mood scale and scores on indices of participation in physical and passive activities. RESULTS: There was no correlation between "night sleep" and the factor scores derived from the neuropsychological tests. "Day sleep" was correlated with "cerebral efficiency" only. Age was correlated with the "memory" and "motor" factors, the latter also being associated with participation in physical activities. CONCLUSION: Night sleep problems are not associated with neuropsychological deficits in a non-clinic population.

Affect↗
PubMed1992

Sleep-disordered breathing in elderly people and subjective sleep-wake disturbance.

Sleep-disordered breathing and subjective reports of sleep-wake disturbances are both common in elderly people but previous studies investigating the relationship between the two have produced uncertain results. We hypothesized that there is no relationship between sleep-disordered breathing and subjective reports of sleep-wake disturbance. Ninety-three random-sampled retirement-village residents, mean age 77.6 years, were monitored overnight with a portable microprocessor-based system. The respiratory disturbance index (RDI) was used as a measure of sleep-disordered breathing. Subjects were interviewed regarding sleep-wake patterns and snoring history and the Mini Mental State Examination, Geriatric Depression Scale and Nelson Adult Reading Test were administered. The sleep-wake responses were entered into a principal components analysis. Two components, reflecting night-time and daytime disturbance, accounted for 34% of the variance. Multiple regression analyses were performed using RDI as a continuous dependent variable, and three predictor variables, night-time, and daytime disturbance and history of snoring. Together, these variables accounted for only 2% of the variance. We conclude there is no relationship between mild and moderate sleep-disordered breathing and subjective sleep-wake disturbance in this population.

Aged↗
PubMed1992

Biotypes of Haemophilus parainfluenzae from the respiratory secretions in chronic bronchitis.

A total of 2401 isolates of Haemophilus parainfluenzae was isolated from respiratory secretions of 36 healthy adults and 128 patients with chronic bronchitis over a period of 1 year. The isolates were allocated to eight biotypes, by their production of indole, urease and ornithine decarboxylase. Biotypes I and II constituted most of the isolates of H. parainfluenzae from the oropharynx of controls (75%) and chronic bronchitics (c. 90%). Among the patients, there was no difference in the isolation rate between oropharyngeal swabs and sputum specimens. Biotypes III, IV, VI, VII and VIII were isolated less frequently, as was a new taxon defined here as biotype V which does not produce indole, urease or ornithine decarboxylase. Biotype III was isolated significantly less frequently from cases of chronic bronchitis than from controls, whereas biotype II was isolated somewhat more frequently from the patients, especially during acute episodes.

Adult↗
PubMed1992

Further evidence that genotypically closely related strains of Legionella pneumophila can express different serogroup specific antigens.

The relationship between serogroup and genotype of Legionella pneumophila strains was investigated by restriction fragment length polymorphism (RFLP) typing with a previously standardised method. Of the 51 RFLP types identified, 19 comprised strains of more than one serogroup. Several RFLP types included strains of five or more serogroups. To determine if sharing the same RFLP type indicates that strains are genotypically indistinguishable or merely that they are superficially similar, 31 strains were selected for further analysis with an extended range of restriction endonucleases and nucleic acid probes. In some cases, strains of a particular RFLP type were indistinguishable, while in others the restriction fragment patterns showed minor differences. It is possible that in the latter case the strains are diverging representatives of a parent clone. We conclude that analysis of restriction fragment patterns, either probed or unprobed, provides a more accurate measure of the ancestral relationship between strains than can be obtained with serological methods.

Antigens, Bacterial↗
PubMed1992

A second serogroup of Legionella erythra serologically indistinguishable from Legionella rubrilucens.

Twenty-two red-autofluorescent Legionella strains were identified serologically as either Legionella rubrilucens or L. erythra. A rRNA probe was used for restriction fragment length polymorphism (RFLP) analysis of the strains and the patterns generated were used as an additional method of identifying the strains to species level. In two instances strains which were identified as L. rubrilucens by serology appeared to belong to the species L. erythra by RFLP analysis. This apparent contradiction was resolved by measurements of DNA/DNA homology which confirmed the existence of a second serogroup of L. erythra serologically indistinguishable from L. rubrilucens.

DNA, Bacterial↗
PubMed1992

Expression of a preprorelaxin-like gene during squamous differentiation of rabbit tracheobronchial epithelial cells and its suppression by retinoic acid.

Squamous cell differentiation in tracheobronchial epithelial cells is accompanied by many biochemical and molecular changes. One of the molecular changes in rabbit tracheal epithelial (RbTE) cells is the differential expression of a squamous cell-specific mRNA encoded by the complementary DNA SQ10. In this study, we sequenced SQ10 complementary DNA and showed that this gene encodes a preprorelaxin-like protein. The DNA sequence of the coding region of SQ10 has 68% identity with the human preprorelaxin mRNA, whereas the deduced amino acid sequence exhibits 46% identity with human preprorelaxin. An antiserum (pepIV-Ab) was raised against a synthetic 22-amino acid oligopeptide of the protein encoded by SQ10. Immunoblot analysis of cellular extracts of squamous-differentiated cells showed that this antiserum reacted with proteins of 22 and 20 kilodaltons, possibly constituting prepro- and proforms of this protein. These proteins were undetectable in undifferentiated RbTE cells. In agreement with these observations, PepIV-Ab specifically stained the cytosol of squamous-differentiated RbTE cells but failed to stain undifferentiated cells. PepIV-Ab recognized a 20 and 16 kilodalton polypeptide in medium conditioned by squamous-differentiated RbTE cells, indicating that the prorelaxin-like protein is secreted. The amino acid sequences of three peptides that were obtained after tryptic digestion of the secreted 16 kilodalton protein were identical to sequences encoded by SQ10. Retinoids which have been shown to inhibit squamous differentiation suppressed the induction of SQ10 protein as well as mRNA in a concentration-dependent manner. The concentration at which retinoic acid caused a 50% inhibition of SQ10 mRNA levels was approximately 5 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Direct amplification and sequencing of the 16S ribosomal DNA of an intracellular Legionella species recovered by amoebal enrichment from the sputum of a patient with pneumonia.

DNA coding for the 16S rRNA of an intracellular bacterium was directly amplified from lysed cells of a host amoebae using the polymerase chain reaction and primers specific for eubacteria. The amoebae had been used to recover an uncultured bacterium observed in the sputum of a patient with pneumonia. The amplified DNA was sequenced directly and compared with published 16S rRNA sequences. The analysis revealed that the intracellular bacterium is a member of the genus Legionella and that it is different from species, including L. pneumophila, for which 16S ribosomal RNA sequence data are available.

Acanthamoeba↗
PubMed1991

Taxonomic considerations of Bartonella bacilliformis based on phylogenetic and phenotypic characteristics.

The 16S-rRNA gene of Bartonella bacilliformis was amplified using the polymerase-chain reaction (PCR). The amplification product was sequenced using a linear-PCR procedure and compared with other published 16S-rRNA sequences. The results of this analysis placed B. bacilliformis in the alpha subgroup of the proteobacteria, and more specifically demonstrated its close phylogenetic relationship to Rochalimaea quintana. This relationship is supported by similarities in the size and mean base composition of the genomes of the two species, and by shared phenotypic characteristics.

Bartonella↗
PubMed1991

Disorders of movement and behaviour during sleep.

OBJECTIVE: To outline recently described movement disorders during sleep which are common and poorly recognised. DATA SOURCES: Computer-based literature search up to July 1990 (with the index terms sleep disorders, sleep myoclonus, nocturnal myoclonus, periodic movements in sleep, REM behaviour disorder and parasomnias) supplemented by a manual search through the references of papers obtained by computer search and a manual search through contents of the following journals: Sleep, Sleep Research, Neurology and Brain. DATA SYNTHESIS AND CONCLUSION: There is a group of common and poorly recognised movement disorders during sleep. The patient usually presents complaining of disturbed sleep, daytime somnolence and abnormal nocturnal behaviour. These conditions are susceptible to precise diagnosis and effective treatment.

Epilepsy↗
PubMed1991

Pressure-volume properties of the upper airway in man.

We report a method of measuring the static pressure-volume properties of the upper airway in unanesthetised humans. In 10 normal subjects the pressure in the upper airway was measured during aspiration of air in 10 ml decrements from 30-40 ml above resting volume to 30-40 ml below resting volume, with the glottis closed voluntarily and the oro-pharyngeal muscles relaxed. The pressure-volume properties of the upper airway were well described by the pressure-volume rate upper airway elastance (UAE, cmH2O/ml). The mean (+/- 95% CI) UAE measured at near total lung capacity and with the neck in neutral position for all runs in all subjects was 0.22 +/- 0.06 cmH2O/ml. When UAE was measured repeatedly on different days the greatest change observed was from a mean value of 0.17 cmH2O/ml on one day to 0.25 cmH2O/ml on another, and the standard deviation of the means from different days ranged from 0.01 to 0.04. Neither hypoxia (SaO2 80-85%) nor hyperoxic hypercapnia (PETCO2 65-75 mmHg) had any influence on UAE. Maximal extension of the neck did not affect UAE, but flexion of the neck was associated with a rise in UAE from a mean of 0.23 +/- 0.05 cmH2O/ml to a mean of 0.53 +/- 0.14 cmH2O/ml. UAE was not affected by the lung volume at which measurements were made. We conclude that upper airway pressure-volume properties can be measured non-invasively in man, and that in their linearity, reproducibility and lack of sensitivity to hypoxia and hypercapnia they resemble those of experimental animals.

Adult↗
PubMed1991

Mechanical properties of the rabbit upper airway during hypoxia and hypercapnia.

It has been suggested that the response of upper airway muscles to hypoxia may be different from the response of these muscles to hypercapnia. We therefore measured pulmonary ventilation and the mechanical properties of the isolated upper airway in 9 anesthetised rabbits during respiration of hypoxic and hypercapnic gas mixtures. Each animal was exposed to several levels of elevated inspiratory CO2 fraction, FICO2 (0.03 to 0.17) and depressed inspiratory O2 fraction, FIO2 (0.19 to 0.09). The steady-state ventilatory response, the tidal pressure in the upper airway (PTUA) and the upper airway elastance were measured under each condition. Straight lines were calculated by least squares regression relating pulmonary VT to FICO2 and FIO2 and PTUA to FICO2 and FIO2. The PTUA was estimated graphically at two levels of hypoxia and hypercapnia producing equal augmentation of VT. The ratio of PTUA during hypoxia to PTUA during hypercapnia was 1.06 +/- 0.21 (mean +/- 95% C.I.) at low VT and 1.15 +/- 0.25 at high VT. Elastance of the upper airway rose from 6.25 +/- 1.13 cmH2O/ml under control conditions to a maximum of 7.95 +/- 1.24 cmH2O/ml (P less than 0.05) during hypercapnia and to a maximum of 8.02 +/- 1.17 cmH2O/ml (P less than 0.05) during hypoxia. There was no difference between the mean (+/- 95% C.I.) change associated with hypercapnia (1.64 +/- 1.08 cmH2O/ml) and the mean change associated with hypoxia (1.77 +/- 1.26 cmH2O/ml). We concluded that hypoxia did not result in a greater change in upper airway mechanical properties than hypercapnia.

Animals↗